Puma cancer med short review time bad sign from FDA?

April 21, 2017

The U.S. Food and Drug Administration (FDA) has scheduled its Oncologic Drugs Advisory Committee (ODAC) meeting for Puma Biotechnology (PBYI)’s neratinib for May 24. Adam Feuerstein, writing for TheStreet, notes that the committee’s Rick Pazdur has only scheduled five hours for the meeting, which he feels is bad news for Puma—although he also notes opposing opinions on the matter.

Neratinib is an investigational drug for the extended adjuvant treatment of early stage HER2-positive breast cancer that has previously been treated with a trastuzumab containing regimen. The committee will evaluate the company’s New Drug Application (NDA) for the drug based on results from the Phase III ExteNET clinical trial and Phase II CONTROL trial.

Feuerstein writes, “If FDA history is a guide, an abbreviated turn in front of a panel of outside experts spells a bad outcome for Puma. Over the past five years, Pazdur has often used half-day sessions of the FDA Oncologic Drugs Advisory Committee (ODAC) to administer public floggings to flawed cancer drugs.”

The FDA’s PDUFA date for the NDA is July 21, but that will await the recommendation of the ODAC committee, led by Pazdur.

The Phase III ExteNET trial showed the drug had a two-year disease-free survival (DFS) rate of 93.9 percent compared with 91.6 percent in the placebo group. The NDA was originally planned for the first quarter of 2016, but was delayed after the FDA requested a new statistical analysis of the ExteNET trial data. That analysis, according to OncLive, “data were censored for patients who missed two or more scheduled disease assessments prior to recurrence or death.”

After that analysis, the two-year invasive DFS rates were 94.2 percent and 91.9 percent for neratinib and placebo, respectively.

“The FDA requested that Puma include the results of this phase II trial that incorporated the loperamide prophylaxis with the NDA filing and stated that the potential to include this data in the label for neratinib would be a review issue and part of the labeling negotiation,” said Alan Auerbach, Puma’s chief executive officer and president in a statement from March 2016, when the delay was announced.

According to Feuerstein, analysts and investors bullish on Puma argue that the shortened ODAC committee hearing means the FDA doesn’t have many problems with the drug’s data. Feuerstein’s argument is based on precedent. “Over the past five years,” he writes, “Pazdur has brought together the FDA and its ODAC experts for 12 half-day sessions where cancer drugs were reviewed and voted on. At eight of these sessions—two-thirds of the time—the FDA was sharply critical of the cancer drugs being reviewed, leading to ODAC panel votes against approval.”